Malaria remains a formidable challenge to global health, claiming the lives of nearly half a million individuals annually despite vigorous efforts to curb its spread. Among the myriad factors influencing the persistence and virulence of this disease, the role of specific proteins during the Plasmodium development cycle is critical. The protein of interest, Pfs16, is a Parasitophorous Vacuole Membrane Protein expressed from the earliest asexual stages, which encompass the development of Plasmodium falciparum in the host, to the final stage of the parasite's development in the mosquito, the sporozoite, playing a crucial role in this lifecycle. Understanding the function and mechanism of this conserved protein is pivotal for advancing our strategies to combat malaria. In this review, we examine the work on Pfs16 in both the asexual and sexual stages of parasite development, aiming to gain a better understanding of this protein as a promising candidate for drug and vaccine development.